“Gammaherpesvirinae”的意思、由来-开放百科全书

Herpesviruses represent a group of double-stranded DNA viruses distributed widely within the animal kingdom. The family Herpesviridae, which contains eight viruses that infect humans, is the most extensively studied group within this order and comprises three subfamilies, namely Alphaherpesvirinae, Betaherpesvirinae and Gammaherpesvirinae. Gammaherpesviruses belong to four separate genera: the well-established genera Lymphocryptovirus and Rhadinovirus and the more recently defined genera Macavirus and Percavirus.

Gammaherpesviruses are of primary interest due to the two human viruses, EBV and KSHV and the diseases they cause.The gammaherpesviruses replicate and persist in lymphoid cells but some are capable of undergoing lytic replication in epithelial or fibroblast cells. Gammaherpesviruses may be a cause of chronic fibrotic lung diseases in humans and in animals.^[3]

These viruses can be subdivided into two genera: lymphocryptoviruses (gamma-1) and rhadinoviruses (gamma-2):

Taxonomy

Structure

Viruses in Gammaherpesvirinae are enveloped, with icosahedral, spherical to pleomorphic, and round geometries, and T=16 symmetry. The diameter is around 150-200 nm. Genomes are linear and non-segmented, around 180kb in length.^[1]

Virus Life cycle

• Primary envelopment, invaginations of nuclear membrane(s) and nuclear egress

Lytic Cycle

The lytic cycle of the gammaherpesviruses is initiated only on rare occasions (Oehmig et al., 2004). Therefore, the least contribution to pathogenicity has to be expected from this stage. The ORFs expressed during that stage are further divided into immediate-early, early, and late. Promoter activation mediated by these proteins has also a strong effect on DNA synthesis from the origins of lytic DNA replication. As a result, virions are generated and released from the productively infected cells.^[9]

Growth De-regulating genes of Gammaherpesvirus

Herpesviruses have large genomes containing a wide array of genes. Although the first ORF in these gammaherpesviruses have oncogenic potential, other viral genes may also play a role in viral transformation. A striking feature of the four gammaherpesviruses is that they contain distinct ORFs involved in lymphocyte signaling events. At the left end of each viral genome are located ORFs encoding distinct transforming proteins.The Gammaherpes viral genes are capable of modulating cellular signals such that cell proliferation and viral replication occur at the appropriate times in the viral life cycle.^[4]

Immune evasion strategies

Viruses that establish lifelong latent infections must ensure that the viral genome is maintained within the latently infected cell throughout the life of the host, yet at the same time must also be capable of avoiding elimination by the immune surveillance system especially must avoid being detected by host CD8+ cytotoxic T lymphocytes (CTLs). The gamma-herpesviruses are characteristically latent in lymphocytes and drive the proliferation that requires the expression of latent viral antigens.^[10] The majority of gammaherpesviruses encode a specific protein that is critical for maintenance of the viral genome within latently infected cells termed the genome maintenance protein (GMP). GMPs are DNA-binding proteins that ensures that, as the host cell progresses through mitosis, the viral episomes are partitioned to daughter cells. This provides continuous existence of the viral genome within the host cells.^[4]

Vaccines

Attenuated virus mutants represent a promising approach towards gamma-herpesvirus infection control. Surprisingly, latency-deficient and, therefore, apathogenic MHV-68 mutants are found to be highly effective vaccines against these viruses.^[10] Research in this area is almost exclusively performed using MHV68 as KSHV and EBV (the major human pathogens of this family) do not productively infect model organisms typically used for this type of experimentation.

References

1. ^¹{{cite web|title=Viral Zone|url=http://viralzone.expasy.org/all_by_species/18.html|publisher=ExPASy|accessdate=15 June 2015}}
2. ^¹{{cite web|last1=ICTV|title=Virus Taxonomy: 2014 Release|url=http://ictvonline.org/virusTaxonomy.asp|accessdate=15 June 2015}}
3. ^{{cite journal|last=Williams|first=KJ|title=Gammaherpesviruses and Pulmonary Fibrosis: Evidence From Humans, Horses, and Rodents|journal=Veterinary Pathology|date=March 2014|volume=51|issue=2|pages=372–384|doi=10.1177/0300985814521838|pmid=24569614|url=http://vet.sagepub.com/content/51/2/372.long}}
4. ^¹²{{Cite journal | last1 = Blake | first1 = N. | title = Immune evasion by gammaherpesvirus genome maintenance proteins | doi = 10.1099/vir.0.018242-0 | journal = Journal of General Virology | volume = 91 | issue = 4 | pages = 829–846 | year = 2010 | pmid = 20089802 | pmc = }}
5. ^Nagamine B, Jones L, Tellgren-Roth C, Cavender J, Bratanich AC (2011) A novel gammaherpesvirus isolated from a black-tailed prairie dog (Cynomys ludovicianus). Arch Virol
6. ^Wellehan JF, Johnson AJ, Childress AL, Harr KE, Isaza R (2008) Six novel gammaherpesviruses of Afrotheria provide insight into the early divergence of the Gammaherpesvirinae. Vet Microbiol 127(3-4):249-257
7. ^Davison AJ, Subramaniam K, Kerr K, Jacob JM, Landrau-Giovannetti N, Walsh MT, Wells RS, Waltzek TB (2017) Genome sequence of a gammaherpesvirus from a common bottlenose dolphin (Tursiops truncatus). Genome Announc 5(31)
8. ^{{Cite journal | last1 = Peng | first1 = L. | last2 = Ryazantsev | first2 = S. | last3 = Sun | first3 = R. | last4 = Zhou | first4 = Z. H. | title = Three-Dimensional Visualization of Gammaherpesvirus Life Cycle in Host Cells by Electron Tomography | doi = 10.1016/j.str.2009.10.017 | journal = Structure | volume = 18 | issue = 1 | pages = 47–58 | year = 2010 | pmid = 20152152 | pmc =2866045 }}
9. ^{{Cite journal | last1 = Ackermann | first1 = M. | title = Pathogenesis of gammaherpesvirus infections | doi = 10.1016/j.vetmic.2005.11.008 | journal = Veterinary Microbiology | volume = 113 | issue = 3–4 | pages = 211–222 | year = 2006 | pmid = 16332416 | pmc = }}
10. ^¹{{Cite journal | last1 = Stevenson | first1 = P. G. | title = Immune evasion by gamma-herpesviruses | doi = 10.1016/j.coi.2004.05.002 | journal = Current Opinion in Immunology | volume = 16 | issue = 4 | pages = 456–462 | year = 2004 | pmid = 15245739 | pmc = }}

Classification